The United States is in the middle of an unprecedented cocaine abuse epidemic. Over 22 million Americans are estimated to have used cocaine and the impact of this dramatic increase is now becoming evident. There is currently a paucity of information on the behavioral effects of the chronic use of cocaine, the degree of tolerance which develops, and the presence or absence of withdrawal signs upon abrupt discontinuation of cocaine. This lack of information extends to the effects of cocaine on cardiovascular function at doses which produce behavioral effects. It is speculated that the cardiovascular effects may contribute to cocaine related medical emergencies and lethality. Frequently, cocaine is abused simultaneously with other behaviorally active drugs. Such combinations as cocaine and narcotics, cocaine and amphetamines, and cocaine and marijuana are frequently used and the resultant effects are essentially unknown. This project will attempt to provide answers to some of these questions by studying the effects of cocaine alone in the squirrel monkey before, during, and after chronic administration of cocaine, and in combination with four other drugs which are likely to be co-abused with cocaine: morphine, d-amphetamine, Delta-9-tetrahydrocannabinol, and caffeine. The effects of cocaine and cocaine combined with selected doses of the other four drugs will be determined on responding under a multiple fixed-interval (food), fixed-interval (escape) schedule of reinforcement. During the behavioral sessions, cardiovascular function (blood pressure, heart rate, and EKG), and core body temperature will be recorded. In addition, the pharmacokinetics of cocaine will be determined before and during the chronic administration of cocaine. These experiments will provide information on the degree of tolerance development or increased sensitivity as a result of the chronic dosing, the extent of withdrawal signs upon the abrupt discontinuation of chronic cocaine administration, and the nature of the interactions which occur as a result of combined administration of cocaine and other drugs of abuse. In addition, it will be possible to determine the contribution of any changes in cocaine disposition kinetics in the changes observed in the cocaine dose-response curves as a result of chronic dosing.